The experiments outlined in this research proposal have been designed to improve our understanding of the origins and mechanisms of action of E. coli mutator genes. The aims of the proposed research are two-fold. Our short-term goal is an understanding of those events involved in DNA replication and repair that can cause errors; our long- term goal is an understanding of the role that mutation plays in evolution. Detailed procedures are discussed for isolating and characterizing new mutator genes, and for studying their involvement in DNA replication.